22 Hematopoietic Stem Cell Transplantation Chow Flashcards
What are the goals of Pre-Transplant Conditioning (“Negative Days” to Day 0)?
To eradicate as many malignant cells as possible before re-infusion of stem cells. To suppress recipient’s immune system prior to receiving donor stem cells (allHSCT)
What are the Immunological Sources of Stem Cells?
Autologous HSCT (recipient’s own stem cells collected previously). Syngeneic HSCT (identical twin’s stem cells). Allogeneic HSCT (donor provides stem cells)
What are the different types of Allogeneic HSCT?
Matched related donor (MRD). Mismatched related donor (MMRD). Matched unrelated donor (MUD). Mismatched unrelated donor (MURD)
What is Allogeneic HSCT: HLA Matching?
Human Leukocyte Antigen (HLA) encodes the Major Histocompatibility Complex (MHC) genes, which are surface antigens important for compatibility between donor stem cells and host tissues. Matching of HLA-A, -B, and -DR the most critical
What is Nonmyeloablative Transplantation (NMT; “mini-allo”)?
Chemotherapy used in conditioning regimen may not completely eliminate tumor cells. Role of conditioning regimen is to immuno-suppress recipients to allow for engraftment of donor stem cells. Rationale: utilizes donor T-cell mediated graft-versus-tumor (GVT) effect that continues to eradicate recipient tumor cells post transplant. This allows the use of stem cell transplantation in elderly patients and/or those who cannot tolerate high dose intensive conditioning regimens
Which source of stem cells are less likely to develop chronic GVHD?
Bone Marrow
Which source of stem cells is most common but also has a high risk of chronic GVHD?
Peripheral blood
What are Peripheral Stem Cell Mobilization agents used for?
To increase the number of CD34+ stem cells that can be collected by leukapheresis of peripheral blood
What are the commonly used Peripheral Stem Cell Mobilization agents?
Filgrastim. Sargramostim
What is Plerixafor (Mozobil)?
CXCR4 chemokine receptor inhibitor. Mobilizes hematopoietic stem cells to peripheral blood to be collected for autologous transplantation for multiple myeloma and NHL
What are the complications with HSCT?
Infection! GVHD! Mucositis! Hematologic toxicities - expected from conditioning regimen. Non-hematologic toxicities: Pulmonary, hepatic, renal, cardiac toxicities, Hepatic veno-occlusive disease, Microangiopathy
What are some Post-Transplant Complications?
Toxicities related to conditioning regimen (Nephrotoxicity (cisplatin, ifosfamide), Hepatotoxicity (busulfan, carboplatin), Cardiotoxicity (cyclophosphamide), Mucositis (etoposide, melphalan, TBI)
What is Mucositis commonly caused by?
Etp[psode, Melphalan, TBI
What are Post-Transplant Infections like?
High risk due to neutropenia, mucositis, immunodeficiency, and central line catheters. Highest risk before engraftment (time of sustained ANC/platelet count without need for transfusion)
What is Graft-Versus-Host Disease?
Antigens on host cells activate T-lymphocytes of donor cells, which mount immunologic “attack” on host tissues. Primarily with allogenous HSCT. Staging/grading based on skin, gut, and liver toxicities
What is Acute GVHD (< 100 days post transplant)?
Incidence ~25-70%. Risk factors: HLA mismatch, gender mismatch (F:M > F:F > M:M). Older age. Advanced disease stage. High dose of infused stem cells
What is used for prevention of acute GVHD?
Start immunosuppression after conditioning chemotherapy is complicated. Choice of immunosuppressant(s) is dependent on the conditioning regimen per institutional protocols
What are some common agents used for Prevention of Acute GVHD?
Tacrolimus, Sirolimus, Methotrexate, Cyclosporine
What is 1st line treatment for Acute GVHD?
Methylprednisolone! Prednisone, Daclizumab, Infliximab, Beclomethasone
What is Chronic GVHD?
> 100 days post transplant. Risk factors: h/o GVHD, HLA mismatch, gender mismatch, older recipient, PBSC
What is Limited Chronic GVHD?
Either or both: 1) Localized skin involvement, 2) Hepatic dysfunction d/t chronic GVHD
What is Extensive Chronic GVHD?
Either: 1) Generalized skin involvement, or 2) Localized skin involvement and/or hepatic dysfunction d/t chronic GVHD. PLUS. 3a) Liver histology showing chronic aggressive hepatitis, bridging necrosis, or cirrhosis, or 3b) Involvement of eye, or 3c) Involvement of minor salivary glands or oral mucosa demonstrated on labial biopsy, or 3d) Involvement of any other target organ
What is done for treatment of Chronic GVHD?
Treat cGVHD that involves > 3 organs or if > Grade 2 severity in any one organ.
What agents are used for treatment of Chronic GVHD?
Prednisone QOD! Prednisone alternating with Cyclosporine QOD. Organ-specific supportive care treatment
